BCAT1

BCAT1
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	2ABJ, 2COG, 2COI, 2COJ
Identifikatori
Aliasi	BCAT1
Vanjski ID-jevi	OMIM: 113520 MGI: 104861 HomoloGene: 20320 GeneCards: BCAT1
Lokacija gena (čovjek)
Hrom.	Hromosom 12 (čovjek)
Kraj	24,949,101 bp
Lokacija gena (miš)
Hrom.	Hromosom 6 (miš)
Kraj	145,021,910 bp
Ontologija gena
Molekularna funkcija	• transaminase activity; • L-leucine transaminase activity; • vezivanje identičnih proteina; • catalytic activity; • L-valine transaminase activity; • L-isoleucine transaminase activity; • aktivnost sa transferazom; • branched-chain-amino-acid transaminase activity;
Ćelijska komponenta	• citoplazma; • mitohondrija; • citosol;
Biološki proces	• metabolizam; • branched-chain amino acid biosynthetic process; • Ćelijska proliferacija; • cellular amino acid biosynthetic process; • branched-chain amino acid metabolic process; • leucine biosynthetic process; • branched-chain amino acid catabolic process; • valine biosynthetic process; • G1/S transition of mitotic cell cycle;
	Izvori:Amigo / QuickGO
Ortolozi
	586
	12035
	ENSG00000060982
	ENSMUSG00000030268
	P54687
	P24288
	NM_001178091; NM_001178092; NM_001178093; NM_001178094; NM_005504
	NM_001024468; NM_007532
	NP_001171562; NP_001171563; NP_001171564; NP_001171565; NP_005495
	NP_001019639; NP_031558
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Transaminaza 1 razgranatih aminokiselinskih lanaca je protein-enzim koji je kod ljudi kodiran genom BCAT1.^[5] To je prvi enzim na putu razgradnje aminokiselina razgranatog lanca (BCAA) i olakšava reverzibilnu transaminaciju BCAA i glutamata. BCAT1 se nalazi u citoplazmi, dok se njegova izoforma, BCAT2 nalazi u mitohondrijama.

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 386 aminokiselina, a molekulska težina 42.966 Da.^[6].

10	20	30	40	50
MKDCSNGCSA	ECTGEGGSKE	VVGTFKAKDL	IVTPATILKE	KPDPNNLVFG
TVFTDHMLTV	EWSSEFGWEK	PHIKPLQNLS	LHPGSSALHY	AVELFEGLKA
FRGVDNKIRL	FQPNLNMDRM	YRSAVRATLP	VFDKEELLEC	IQQLVKLDQE
WVPYSTSASL	YIRPTFIGTE	PSLGVKKPTK	ALLFVLLSPV	GPYFSSGTFN
PVSLWANPKY	VRAWKGGTGD	CKMGGNYGSS	LFAQCEAVDN	GCQQVLWLYG
EDHQITEVGT	MNLFLYWINE	DGEEELATPP	LDGIILPGVT	RRCILDLAHQ
WGEFKVSERY	LTMDDLTTAL	EGNRVREMFG	SGTACVVCPV	SDILYKGETI
HIPTMENGPK	LASRILSKLT	DIQYGREESD	WTIVLS

C: Cistein

D: Asparaginska kiselina

E: Glutaminska kiselina

F: Fenilalanin

G: Glicin

H: Histidin

I: Izoleucin

K: Lizin

L: Leucin

M: Metionin

N: Asparagin

P: Prolin

Q: Glutamin

R: Arginin

S: Serin

T: Treonin

V: Valin

W: Triptofan

Y: Tirozin

Funkcija

Ovaj gen kodira citosolni oblik enzim transaminaze aminokiselina razgranatog lanca. Ovaj enzim katalizira reverzibilne transaminacije alfa-keto kiselina razgranatog lanca (BCKA) u aminokiseline razgranatog lanca (BCAA) valin, leucin i izoleucin , koji su neophodni za rast ćelija. Kod ljudi, njegova primarna uloga je deaminacija BCAA, jer im nedostaju enzimi za sintezu BCKA de novo. Odgovarajući kofaktori su alfa-ketoglutarat i glutamat. Odgovarajuće reakcije su:

L-leucin + 2-oksoglutarat = 4-metil-2-oksopentanoat + L-glutamat

L-izoleucin + 2-oksoglutarat = (S)-3-metil-2-oksopentanoat + L-glutamat

L-valin + 2-oksoglutarat = 3-metil-2-oksobutanoat + L-glutamat^[7]

Ćelije mogu dalje razgraditi BCKA pomoću kompleksa dehidrogenaze keto-kiseline s razgranatim lancem iz kojeg ugljikove okosnice svakog BCAA mogu ući u različite puteve razgradnje.^[8]

Često se izvještava da onkogeni transkripcijski faktor Myc podstiče ekspresiju BCAT1.^[9]^[10]^[11]

Klinički značaj

Dva različita klinička poremećaja pripisana su defektu transaminacije aminokiselina razgranatog lanca: hipervalinemija i hiperleucin-izoleucinemija.^[12] Budući da postoji i gen koji kodira mitohondrijski oblik ovog enzima (BCAT2), mutacije oba gena mogu pridonijeti ovim poremećajima.

Prekomjerna ekspresija BCAT1 povezana je s različitim tipovima karcinoma, među njima glioblastomom,^[13] rakom dojke,^[14] akutnom mijeloidnom leukemijom,^[15] rakom želuca^[16] i hroničnom mijeloidnom leukemijom.^[17]

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000060982 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000030268 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Entrez Gene: Branched chain amino acid transaminase 1". Pristupljeno 21. 4. 2016.
^ "UniProt, P54687". Pristupljeno 7. 8. 2021.
^ "BCAT1 - Branched-chain-amino-acid aminotransferase, cytosolic - Homo sapiens (Human) - BCAT1 gene & protein". www.uniprot.org (jezik: engleski). Pristupljeno 6. 8. 2018.
^ "BCKDH in the BCAA degradation pathway". Genome.jp. 6. 8. 2018. Pristupljeno 6. 8. 2018.
^ Zhou W, Feng X, Ren C, Jiang X, Liu W, Huang W, Liu Z, Li Z, Zeng L, Wang L, Zhu B, Shi J, Liu J, Zhang C, Liu Y, Yao K (juni 2013). "Over-expression of BCAT1, a c-Myc target gene, induces cell proliferation, migration and invasion in nasopharyngeal carcinoma". Molecular Cancer. 12: 53. doi:10.1186/1476-4598-12-53. PMC 3698204. PMID 23758864.
^ Schuldiner O, Eden A, Ben-Yosef T, Yanuka O, Simchen G, Benvenisty N (juli 1996). "ECA39, a conserved gene regulated by c-Myc in mice, is involved in G1/S cell cycle regulation in yeast". Proceedings of the National Academy of Sciences of the United States of America. 93 (14): 7143–8. Bibcode:1996PNAS...93.7143S. doi:10.1073/pnas.93.14.7143. PMC 38950. PMID 8692959.
^ Ben-Yosef T, Eden A, Benvenisty N (juli 1998). "Characterization of murine BCAT genes: Bcat1, a c-Myc target, and its homolog, Bcat2". Mammalian Genome. 9 (7): 595–7. doi:10.1007/s003359900825. PMID 9657861. S2CID 21062787.
^ Wang XL, Li CJ, Xing Y, Yang YH, Jia JP (septembar 2015). "Hypervalinemia and hyperleucine-isoleucinemia caused by mutations in the branched-chain-amino-acid aminotransferase gene". Journal of Inherited Metabolic Disease. 38 (5): 855–61. doi:10.1007/s10545-015-9814-z. PMID 25653144. S2CID 24253640.
^ Tönjes M, Barbus S, Park YJ, Wang W, Schlotter M, Lindroth AM, et al. (juli 2013). "BCAT1 promotes cell proliferation through amino acid catabolism in gliomas carrying wild-type IDH1". Nature Medicine. 19 (7): 901–908. doi:10.1038/nm.3217. PMC 4916649. PMID 23793099.
^ Thewes V, Simon R, Hlevnjak M, Schlotter M, Schroeter P, Schmidt K, et al. (juli 2017). "The branched-chain amino acid transaminase 1 sustains growth of antiestrogen-resistant and ERα-negative breast cancer". Oncogene. 36 (29): 4124–4134. doi:10.1038/onc.2017.32. PMID 28319069. S2CID 25098058.
^ Raffel S, Falcone M, Kneisel N, Hansson J, Wang W, Lutz C, et al. (novembar 2017). "BCAT1 restricts αKG levels in AML stem cells leading to IDHmut-like DNA hypermethylation". Nature. 551 (7680): 384–388. Bibcode:2017Natur.551..384R. doi:10.1038/nature24294. PMID 29144447. S2CID 205261267.
^ Xu Y, Yu W, Yang T, Zhang M, Liang C, Cai X, Shao Q (maj 2018). "Overexpression of BCAT1 is a prognostic marker in gastric cancer". Human Pathology. 75: 41–46. doi:10.1016/j.humpath.2018.02.003. PMID 29447920.
^ Hattori A, Tsunoda M, Konuma T, Kobayashi M, Nagy T, Glushka J, Tayyari F, McSkimming D, Kannan N, Tojo A, Edison AS, Ito T (maj 2017). "Cancer progression by reprogrammed BCAA metabolism in myeloid leukaemia". Nature. 545 (7655): 500–504. Bibcode:2017Natur.545..500H. doi:10.1038/nature22314. PMC 5554449. PMID 28514443.

Dopunska literatura

Yoshikawa R, Yanagi H, Shen CS, Fujiwara Y, Noda M, Yagyu T, Gega M, Oshima T, Yamamura T, Okamura H, Nakano Y, Morinaga T, Hashimoto-Tamaoki T (septembar 2006). "ECA39 is a novel distant metastasis-related biomarker in colorectal cancer". World Journal of Gastroenterology. 12 (36): 5884–9. doi:10.3748/wjg.v12.i36.5884. PMC 4100673. PMID 17007058.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000060982 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000030268 - Ensembl, maj 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrez-5] "Entrez Gene: Branched chain amino acid transaminase 1". Pristupljeno 21. 4. 2016.

[UniProt-6] "UniProt, P54687". Pristupljeno 7. 8. 2021.

[7] "BCAT1 - Branched-chain-amino-acid aminotransferase, cytosolic - Homo sapiens (Human) - BCAT1 gene & protein". www.uniprot.org (jezik: engleski). Pristupljeno 6. 8. 2018.

[8] "BCKDH in the BCAA degradation pathway". Genome.jp. 6. 8. 2018. Pristupljeno 6. 8. 2018.

[9] Zhou W, Feng X, Ren C, Jiang X, Liu W, Huang W, Liu Z, Li Z, Zeng L, Wang L, Zhu B, Shi J, Liu J, Zhang C, Liu Y, Yao K (juni 2013). "Over-expression of BCAT1, a c-Myc target gene, induces cell proliferation, migration and invasion in nasopharyngeal carcinoma". Molecular Cancer. 12: 53. doi:10.1186/1476-4598-12-53. PMC 3698204. PMID 23758864.

[10] Schuldiner O, Eden A, Ben-Yosef T, Yanuka O, Simchen G, Benvenisty N (juli 1996). "ECA39, a conserved gene regulated by c-Myc in mice, is involved in G1/S cell cycle regulation in yeast". Proceedings of the National Academy of Sciences of the United States of America. 93 (14): 7143–8. Bibcode:1996PNAS...93.7143S. doi:10.1073/pnas.93.14.7143. PMC 38950. PMID 8692959.

[11] Ben-Yosef T, Eden A, Benvenisty N (juli 1998). "Characterization of murine BCAT genes: Bcat1, a c-Myc target, and its homolog, Bcat2". Mammalian Genome. 9 (7): 595–7. doi:10.1007/s003359900825. PMID 9657861. S2CID 21062787.

[pmid25653144-12] Wang XL, Li CJ, Xing Y, Yang YH, Jia JP (septembar 2015). "Hypervalinemia and hyperleucine-isoleucinemia caused by mutations in the branched-chain-amino-acid aminotransferase gene". Journal of Inherited Metabolic Disease. 38 (5): 855–61. doi:10.1007/s10545-015-9814-z. PMID 25653144. S2CID 24253640.

[13] Tönjes M, Barbus S, Park YJ, Wang W, Schlotter M, Lindroth AM, et al. (juli 2013). "BCAT1 promotes cell proliferation through amino acid catabolism in gliomas carrying wild-type IDH1". Nature Medicine. 19 (7): 901–908. doi:10.1038/nm.3217. PMC 4916649. PMID 23793099.

[14] Thewes V, Simon R, Hlevnjak M, Schlotter M, Schroeter P, Schmidt K, et al. (juli 2017). "The branched-chain amino acid transaminase 1 sustains growth of antiestrogen-resistant and ERα-negative breast cancer". Oncogene. 36 (29): 4124–4134. doi:10.1038/onc.2017.32. PMID 28319069. S2CID 25098058.

[15] Raffel S, Falcone M, Kneisel N, Hansson J, Wang W, Lutz C, et al. (novembar 2017). "BCAT1 restricts αKG levels in AML stem cells leading to IDHmut-like DNA hypermethylation". Nature. 551 (7680): 384–388. Bibcode:2017Natur.551..384R. doi:10.1038/nature24294. PMID 29144447. S2CID 205261267.

[16] Xu Y, Yu W, Yang T, Zhang M, Liang C, Cai X, Shao Q (maj 2018). "Overexpression of BCAT1 is a prognostic marker in gastric cancer". Human Pathology. 75: 41–46. doi:10.1016/j.humpath.2018.02.003. PMID 29447920.

[17] Hattori A, Tsunoda M, Konuma T, Kobayashi M, Nagy T, Glushka J, Tayyari F, McSkimming D, Kannan N, Tojo A, Edison AS, Ito T (maj 2017). "Cancer progression by reprogrammed BCAA metabolism in myeloid leukaemia". Nature. 545 (7655): 500–504. Bibcode:2017Natur.545..500H. doi:10.1038/nature22314. PMC 5554449. PMID 28514443.

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